This proposal is designed to test further the dopamine (DA) hypothesis of antipsychotic drug (APD) action and focuses upon the measurement of neurochemical correlates of chronic APD treatment. The neurochemical measurement of neurochemical correlates of chronic APD treatment. The neurochemical measures employed reflect the status of the DA system itself (brain HVA and DOPAC, CSF and plasma HVA) or related systems (CSF and plasma GABA, cyclic AMP, and prolactin). The phenomenon of tolerance is used to evaluate the significance of regional differences in DA metabolism in animal brain during chronic APD administration and to relate biochemical measures to clinical effects in clinical studies. A second strategy evaluates effects on the DA system and related produced by lithium, an agent which acts clinically to complement or augment the effects of classical APD.